Functional consequences of a MAPK docking site on human FcγRIIb

Dávid Medgyesi, Rita Sárközi, Gábor Koncz, Krisztina Arató, Györgyi Váradi, Gábor K. Tóth, Gabriella Sármay

Research output: Contribution to journalArticle

Abstract

Type IIb Fcγ receptors (FcγRIIb) have a major role in regulating B cell activation. Upon its co-aggregation with the B cell receptors (BCR) via immune complexes FcγRIIb become phosphorylated on tyrosine within its immunoreceptor tyrosine based inhibitory motif (ITIM) and in turn recruit protein- and inositol phosphatases, inhibiting thereby signal transduction. The intracellular domain of the human FcγRIIb has a membrane proximal motif that is very similar to those of MAPK docking site in MAPK-interacting molecules. Additionally, in contrast to the mouse, a serine residue is located next to this motif that is a potential phosphorylation site for Ser/Thr kinases. Our aim was to study the role of the putative MAPK docking motif on FcγRIIb mediated function. We report here that MAPKs bind to FcγRIIb affinity purified from the detergent extracts of anti-IgM activated and BCR-FcγRIIb co-clustered B cells. We detected extracellular signal regulated kinase (ERK) activity in FcγRIIb immunoprecipitates and identified the bound proteins as 85, 44 and 42kDa ERKs by Western blots. Active ERKs bound to the synthetic peptide representing the putative docking site of FcγRIIb on a Ser/Thr phosphatase dependent manner. The FcγRIIb-associated ERKs may phosphorylate the membrane proximal serine of the receptor. We examined the consequences of serine phosphorylation by comparing the proteins that interact with synthetic peptides comprising the combined sequences of the MAPK docking site and the ITIM either in phosphorylated or in non-phosphorylated forms. The results indicate that phosphorylation on serine modifies the binding of Lyn to FcγRIIb, thus might negatively regulate phosphorylation of ITIM.

Original languageEnglish
Pages (from-to)83-90
Number of pages8
JournalImmunology letters
Volume92
Issue number1-2
DOIs
Publication statusPublished - Mar 29 2004

Keywords

  • B cell
  • FcγRIIb
  • MAPK docking site
  • Regulation
  • Signalling

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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